Administration of group A streptococcal cell wall (SCW) peptidoglycan - polysaccharide complexes induces arthritis, liver fibrosis, and spleen cell anergy in genetically susceptible rodents and provides a model to explore all phases of an immune response and the consequences of its dysregulation. One objective of this research is to identify known and novel molecules expressed during the development of inflammation and we have focused on the chemokine superfamily using in vitro, in vivo and ex vivo approaches. Cultured synovial fibroblasts express specific chemokine genes, including CINC and MCP-1, but not others, under pro-arthropathic conditions, implicating selective recruitment of leukocyte populations. Moreover, by engineering mutated forms of CINC and other chemokines with sequence modifications predicted to produce receptor antagonism (RA), it may be possible to block chemotaxis and control leukocyte accumulation at sites of inflammation. Accumulation of leukocytes at inflammatory sites is also regulated by the process of apoptosis. Apoptosis or cell-assisted suicide is controlled by Th1 and Th2 lymphocyte cytokines and when this control becomes unbalanced, insufficient and/or excessive, leukocyte accumulation may occur. Additional mechanisms which influence the transition from acute to chronic inflammation and the potential for pathologic sequelae include natural killer (NK) cell activity. The NK population appears to transiently suppress inflammation through the generation of TGF- beta, but the suppression cannot be maintained as chronic destructive lesions emerge. Identifying mechanisms to sustain this NK cell dependent immune suppression may enable prevention of arthropathic disease.